The invention also provides siRNA polynucleotides that interfere with expression of chemotherapeutic target polypeptides, such as DHFR, thymidylate synthetase, and topoisomerase.
The combined action of disodium folinate with fluorouracil is the formation of a stable three-component complex consisting of thymidylate synthetase, 5-fluorodeoxyuridine monophosphate and 5,10-methylenetetrahydrofolate.
This results in a more intense block of thymidylate synthetase with increased inhibition of DNA synthesis, resulting in an increase in cytotoxicity compared to that of monotherapy with fluorouracil.
Both of these miRNAs impact cellular proliferation through the p53-miRNA circuit, and interact with dihydrofolate reductase (DHFR) and thymidylate synthase (TS).
High levels of thymidylate synthase may be involved in how certain types of cancer form and respond to treatment.
First, FdUMP and the folate cofactor, N5- 10-methylenetetrahydrofolate, bind to thymidylate synthase (TS) to form a covalently bound ternary complex.
First, FdUMP and the folate cofactor, N5-10-methylenetetrahydrofolate, bind to thymidylate synthase (TS) to form a covalently bound ternary complex.
First, FdUMP and the folate cofactor, N5-10-methylenetetrahydrofolate, bind to thymidylate synthase (TS) to form a covalently bound ternary complex.
The cytotoxicity of methotrexate results from three important actions: inhibition of DHFR, inhibition of thymidylate synthase, and alteration of the transport of reduced folates.
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